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https://www.readbyqxmd.com/read/28807912/safety-and-efficacy-of-mhaa4549a-a-broadly-neutralizing-monoclonal-antibody-in-a-human-influenza-a-challenge-model-a-phase-2-randomized-trial
#1
Jacqueline M McBride, Jeremy J Lim, Tracy Burgess, Rong Deng, Michael A Derby, Mauricio Maia, Priscilla Horn, Omer Siddiqui, Daniel Sheinson, Haiyin Chen-Harris, Elizabeth M Newton, Dimitri Fillos, Denise Nazzal, Carrie M Rosenberger, Maikke B Ohlson, Rob Lambkin-Williams, Hosnieh Fathi, Jeffrey M Harris, Jorge A Tavel
BACKGROUND: MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. Safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV-challenge model. METHODS: One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24-36 hours later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1200, or 3600 mg) or a standard oral dose of oseltamivir...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807905/pulmonary-pharmacokinetics-of-colistin-following-administration-of-dry-powder-aerosols-in-rats
#2
Yu-Wei Lin, Qi Tony Zhou, Yang Hu, Nikolas J Onufrak, Siping Sun, Jiping Wang, Alan Forrest, Hak-Kim Chan, Jian Li
Colistin has been administered via nebulization for the treatment of respiratory tract infections. Recently, dry powder inhalation (DPI) has attracted increasing attention. The current study aimed to investigate the pharmacokinetics (PK) of colistin in epithelial lining fluid (ELF) and plasma following DPI and intravenous (IV) administration in healthy Sprague-Dawley rats. Rats were given colistin as DPI intratracheally (0.66 and 1.32 mg base/kg) or IV injection (0.66 mg base/kg). Histopathological examination of lung tissue was performed at 24 h...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28803492/rifampin-vs-rifapentine-what-is-the-preferred-rifamycin-for-tuberculosis
#3
Omamah Alfarisi, Wael A Alghamdi, Mohammad H Al-Shaer, Kelly E Dooley, Charles A Peloquin
One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them...
August 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28796260/clinical-grade-human-umbilical-cord-derived-mesenchymal-stem-cells-reverse-cognitive-aging-via-improving-synaptic-plasticity-and-endogenous-neurogenesis
#4
Ning Cao, Tuling Liao, Jiajing Liu, Zeng Fan, Quan Zeng, Junnian Zhou, Haiyun Pei, Jiafei Xi, Lijuan He, Lin Chen, Xue Nan, Yali Jia, Wen Yue, Xuetao Pei
Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging brain may be a promising approach for rejuvenating cognitive aging. Here, we sought to study the intervention effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive aging in a murine model of aging...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791262/clinical-characteristics-of-pregnancies-complicated-by-congenital-myotonic-dystrophy
#5
Cheonga Yee, Suk-Joo Choi, Soo-Young Oh, Chang-Seok Ki, Cheong-Rae Roh, Jong-Hwa Kim
OBJECTIVE: Although the conventional prevalence of myotonic dystrophy is 1:8,000, the prevalence in Korean population was recently reported as 1:1,245. With higher domestic result than expected, we aimed to investigate the clinical characteristics of pregnancies complicated by congenital myotonic dystrophy in our institution. METHODS: We have reviewed 11 paired cases of neonates diagnosed with congenital myotonic dystrophy and their mothers between July 2004 and May 2014, with clinical features including maternal history of infertility, prenatal ultrasonographic findings, and neonatal outcomes...
July 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28783756/pkc-epsilon-deficiency-alters-progenitor-cell-populations-in-favor-of-megakaryopoiesis
#6
John C Kostyak, Elisabetta Liverani, Satya P Kunapuli
BACKGROUND: It has long been postulated that Protein Kinase C (PKC) is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCε remains elusive. OBJECTIVE: To delineate the role of PKCε in megakaryopoiesis. APPROACH AND RESULTS: We used a PKCε knockout mouse model to examine the effect of PKCε deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution...
2017: PloS One
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#7
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#8
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770300/phase-i-study-of-veliparib-in-combination-with-gemcitabine
#9
Ronald Stoller, John C Schmitz, Fei Ding, Shannon Puhalla, Chandra P Belani, Leonard Appleman, Yan Lin, Yixing Jiang, Salah Almokadem, Daniel Petro, Julianne Holleran, Brian F Kiesel, R Ken Czambel, Benedito A Carneiro, Emmanuel Kontopodis, Pamela A Hershberger, Madani Rachid, Alice Chen, Edward Chu, Jan H Beumer
BACKGROUND: Veliparib (ABT-888) is an oral PARP inhibitor expected to increase gemcitabine activity. This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine. METHODS: Patients with advanced solid tumors received veliparib (10-40-mg PO BID) on chemotherapy weeks with gemcitabine 500-750-mg/m(2) IV on days 1, 8, and 15 (28-day cycle), or on days 1 and 8 (21-day cycle)...
August 2, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28769004/pharmacokinetic-pharmacodynamic-analysis-for-doripenem-regimens-in-intensive-care-unit-patient
#10
Ryota Tanaka, Yuhki Sato, Koji Goto, Norihisa Yasuda, Yoshifumi Ohchi, Yosuke Suzuki, Tamio Ueno, Kentaro Ito, Tetsuya Kaneko, Shusaku Kurogi, Ko Nonoshita, Hiroki Itoh
Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28769002/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-luseogliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-japanese-patients-with-type-2-diabetes-mellitus
#11
Yoshishige Samukawa, Masaru Mutoh, Shi Chen, Nobuo Mizui
Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by promoting urinary glucose excretion (UGE). A clinical pharmacology study conducted in Japanese patients with T2DM confirmed dose-dependency of UGE with once-daily administration of luseogliflozin; however, the reason for sustained UGE after plasma luseogliflozin decreased was unclear. To elucidate the effect of inhibition rate constants, Kon and Koff, and to explain the sustained UGE, a pharmacokinetic-pharmacodynamic (PK-PD) model was built based on the mechanisms of glucose filtration in the glomerulus and reabsorption in the renal proximal tubule of kidney as well as the kinetics of competitive inhibition of SGLT1/2 and inhibition rate constants of SGLT2, by using UGE and plasma glucose levels and luseogliflozin concentrations...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28767431/correlation-between-protein-kinase-catalytic-subunit-alpha-1-gene-rs13361707-polymorphism-and-gastric-cancer-susceptibility-in-asian-populations
#12
Jianfeng Ni, Nan Shen, Jilei Tang, Kewei Ren
A single nucleotide polymorphism (SNP) of the protein kinase catalytic subunit alpha-1 gene (PRKAA1) that confers susceptibility to gastric cancer (GC) was identified by genome-wide association in several case-control studies. However, the results remained controversial and ambiguous. Therefore, we performed a larger meta-analysis to confirm this association. We searched the PubMed, Embase, WanFang, and CNKI databases, without any restriction on language, covering all papers published until Feb 22, 2017. Overall, 14 case-control studies with 14,485 cases and 14,792 controls were retrieved based on the search criteria...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28764320/lipoteichoic-acid-isolated-from-staphylococcus-aureus-induces-both-epithelial-mesenchymal-transition-and-wound-healing-in-hacat-cells
#13
Seongjae Kim, Hyeoung-Eun Kim, Boyeon Kang, Youn-Woo Lee, Hangeun Kim, Dae Kyun Chung
Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is recognized by toll-like receptor (TLR) 2, expressed on certain mammalian cell surfaces, initiating signaling cascades that include nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK). There are many structural and functional varieties of LTA, which vary according to the different species of gram-positive bacteria which produce them. In this study, we examined whether LTA isolated from Staphylococcus aureus (aLTA) affects the expression of junction proteins in keratinocytes...
August 3, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28764132/use-of-a-simple-pharmacokinetic-model-to-study-the-impact-of-breast-feeding-on-infant-and-toddler-body-burdens-of-pcb-153-bde-47-and-dde
#14
Matthew Lorber, Leisa-Maree L Toms
Several studies have examined the role of breast milk consumption in the buildup of environmental chemicals in infants, and have concluded that this pathway elevates infant body burdens above what would occur in a formula-only diet. Unique data from Australia provide an opportunity to study this finding using simple pharmacokinetic (PK) models. Pooled serum samples from infants in the general population provided data on PCB 153, BDE 47, and DDE at 6-month increments from birth until 4 years of age. General population breast-feeding scenarios for Australian conditions were crafted and input into a simple PK model which predicted infant serum concentrations over time...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28761582/population-pharmacokinetic-characteristics-of-amikacin-in-suspected-cases-of-neonatal-sepsis-in-a-low-resource-african-setting-a-prospective-nonrandomized-single-site-study
#15
Seth K Amponsah, George O Adjei, Christabel Enweronu-Laryea, Kwasi A Bugyei, Kosta Hadji-Popovski, Jorgen A L Kurtzhals, Kim Kristensen
BACKGROUND: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings. OBJECTIVES: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin. METHODS: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28760897/tools-for-the-individualized-therapy-of-teicoplanin-for-neonates-and-children
#16
V Ramos-Martín, M N Neely, K Padmore, M Peak, M W Beresford, M A Turner, S Paulus, J López-Herce, W W Hope
The aim of the study was to develop a population PK model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the constructed software for individualized therapy. We developed a non-parametric population model fitted to PK data from neonates, infants and older children. We then implemented it in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility. It was used to predict the required dosages to achieve teicoplanin optimal pre-dose targets (15 mg/L) from day 3 of therapy...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28752969/-investigation-the-inhibitory-effects-of-kaempferol-on-rat-renalmesangial-cells-proliferation-under-high-glucose-condition
#17
Ni Chen, Peng-Ding Han, Wen Chen, Yan Deng
OBJECTIVE: To investigate the protective effects of kaempferol on rat renal mesangial cells under high glucose condition and explore its mechanism. METHODS: The HBZY-1 cells were divided into normal glucose group (5.5 mmol/L), high glucose group (25 mmol/L), 10 μmol/L kaempferol+high glucose group, and 30 μmol/L kaempferol+high glucose group. Cell proliferative ability was measured by MTT; cell cycle was analyzed by flow cytometry; mRNA and protein levels were determined by Real-time PCR and Western blot, respectively...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28750271/safety-tolerability%C3%A2-and-antitumour-activity-of-ly2780301-p70s6k-akt-inhibitor-in-combination-with-gemcitabine-in-molecularly-selected-patients-with-advanced-or-metastatic-cancer-a-phase-ib-dose-escalation-study
#18
Eric Angevin, Philippe A Cassier, Antoine Italiano, Anthony Gonçalves, Anas Gazzah, Catherine Terret, Maud Toulmonde, Gwenaëlle Gravis, Andrea Varga, Cédric Parlavecchio, Angelo Paci, Vianney Poinsignon, Jean-Charles Soria, Damien Drubay, Antoine Hollebecque
BACKGROUND: LY2780301, a dual inhibitor of protein kinase B (AKT) and the downstream effector p70 ribosomal protein S6 kinase (p70S6K), may inhibit progression in tumours relying on phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signalling pathway activation. This phase IB trial investigated the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetics (PK) and antitumour activity of LY2780301 plus gemcitabine in patients with advanced/metastatic solid tumours...
July 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28749392/evaluation-of-evidence-for-pharmacokinetics-pharmacodynamics-based-dose-optimization-of-antimicrobials-for-treating-gram-negative-infections-in-neonates
#19
REVIEW
Nusrat Shafiq, Samir Malhotra, Vikas Gautam, Harpreet Kaur, Pravin Kumar, Sourabh Dutta, Pallab Ray, Nilima A Kshirsagar
BACKGROUND & OBJECTIVES: Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections...
March 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28749255/pharmacokinetics-of-orally-administered-voriconazole-in-african-penguins-spheniscus-demersus-after-single-and-multiple-doses
#20
Michael W Hyatt, Nathan P Wiederhold, William W Hope, Katharine E Stott
Aspergillosis is a common respiratory fungal disease in African penguins ( Spheniscus demersus ) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials...
June 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
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